1,2-Dimethoxyethane → Cdc7-IN-7c

HRID 1022901Notes

Reaction equation

HRID 1022901 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([CH2:12][N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=[N:5][C:4]=2[CH:3]=1.[CH3:18][C:19]1[C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][N:21](C(OC(C)(C)C)=O)[N:20]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[CH3:18][C:19]1[NH:20][N:21]=[CH:22][C:23]=1[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([CH2:12][N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=[N:5][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 53216815Tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrazole-1-carboxylateHCID 1363339066-bromo-2-(pyrrolidin-1-ylmethyl)thieno[3,2-d]pyrimidin-4(3H)-one

Product 1

HCID 136333907Cdc7-IN-7cYield 43.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

6-Bromo-2-(pyrrolidin-1-ylmethyl)thieno[3,2-d]pyrimidin-4(3H)-one (100 mg), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (294 mg), sodium carbonate (95 mg), 1,2-dimethoxyethane (3.0 mL) and water (1.5 mL) were placed in a flask, and the atmosphere in the flask was purged with argon. [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane complex (1:1) (26 mg) was added, and the atmosphere in the flask was purged again with argon. The reaction system was stirred at 100° C. for 3 hr, 8M aqueous sodium hydroxide solution (1 mL) was added, and the mixture was stirred at 100° C. for 30 min. After stirring, the mixture was extracted with ethyl acetate/tetrahydrofuran mixture, and the extract was dried over anhydrous sodium sulfate. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate/hexane and methanol/ethyl acetate), and the obtained pale-yellow solid was crystallized from methanol/ethyl acetate to give the title compound (44 mg) as a pale-yellow solid.

Workup

  1. customthe atmosphere in the flask was purged with argon
  2. addition[1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane complex (1:1) (26 mg) was added
  3. customthe atmosphere in the flask was purged again with argon
  4. addition8M aqueous sodium hydroxide solution (1 mL) was added
  5. stirringthe mixture was stirred at 100° C. for 30 min
  6. stirringAfter stirring
  7. extractionthe mixture was extracted with ethyl acetate/tetrahydrofuran mixture
  8. dry with materialthe extract was dried over anhydrous sodium sulfate
  9. customInsoluble material was removed by filtration
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by basic silica gel column chromatography (ethyl acetate/hexane and methanol/ethyl acetate)
  12. customthe obtained pale-yellow solid was crystallized from methanol/ethyl acetate

Sources & evidence

ORD record
ord-278c77d8c332495eb0e456e437fceb2b
Source dataset
uspto-grants-2014_05
Patent number
US08722660B2

Reaction notes

Loading…